Comparative Toxicity by Sex Among Children Treated for Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group.

BACKGROUND: Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities. PROCEDURES: We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991. RESULTS: Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5-5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males. CONCLUSIONS: This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice.

Psychological distress and unsatisfied need for psychosocial support in adolescent and young adult cancer patients during the first year following diagnosis.

PURPOSE: Identifying at-risk adolescent and young adult (AYA) cancer patients and referring them to age-appropriate psychosocial support services may be instrumental in reducing psychological distress and promoting psychosocial adaptation. The purpose of this study is to identify trajectories of clinically significant levels of distress throughout the first year following diagnosis and to distinguish factors, including supportive care service use, that predict the extent to which AYAs report distress. METHODS: In this prospective multisite study, 215 AYAs aged 15-39 years were assessed for psychological distress and psychosocial support service use within the first 4 months of diagnosis and again 6 and 12 months later. On the basis of distress scores, respondents were assigned to one of four distress trajectory groups (Resilient, Recovery, Delayed, and Chronic). Multiple logistic regression analyses examined whether demographics, clinical variables, and reports of unsatisfied need for psychosocial support were associated with distress trajectories over 1 year. RESULTS: Twelve percent of AYAs reported clinically significant chronic distress throughout the first 12 months following diagnosis. An additional 15% reported delayed distress. Substantial proportions of AYAs reported that needs for information (57%), counseling (41%), and practical support (39%) remained unsatisfied at 12 months following diagnosis. Not getting counseling needs met, particularly with regard to professional mental health services, was observed to be significantly associated with distress over time. CONCLUSIONS: Substantial proportions of AYAs are not utilizing psychosocial support services. Findings suggest the importance of identifying psychologically distressed AYAs and addressing their needs for mental health counseling throughout a continuum of care.

Psychosocial service use and unmet need among recently diagnosed adolescent and young adult cancer patients.

BACKGROUND: Adolescents and young adults (AYAs) with cancer demonstrate biomedical risks and psychosocial issues distinct from those of children or older adults. In this study, the authors examined and compared the extent to which AYAs treated in pediatric or adult oncology settings reported use of, and unmet need for, psychosocial support services. METHODS: Within 4 months of initial cancer diagnosis, 215 AYAs ages 14 to 39 years (99 from pediatric care settings and 116 from adult care settings; 75% response rate) were assessed for reporting use of information resources, emotional support services, and practical support services. Statistical analyses derived odds ratios and 95% confidence intervals for service use and unmet needs after controlling for race, employment/school status, sex, relationship status, severity of cancer, treatment, and treatment-related side effects. RESULTS: AYAs ages 20 to 29 years were significantly less likely than teens and older patients ages 30 to 39 years to report using professional mental health services and were significantly more likely to report an unmet need with regard to cancer information, infertility information, and diet/nutrition information. Compared with teens who were treated in pediatric facilities, AYAs who were treated in adult facilities were more likely to report an unmet need for age-appropriate Internet sites, professional mental health services, camp/retreats programs, transportation assistance, and complementary and alternative health services. CONCLUSIONS: Substantial proportions of AYAs are not getting their psychosocial care needs met. Bolstering psychosocial support staff and patient referral to community-based social service agencies and reputable Internet resources may enhance care and improve quality of life for AYAs.

Post-traumatic growth among an ethnically diverse sample of adolescent and young adult cancer survivors.

OBJECTIVE: Although some survivors of childhood cancer report significant psychosocial distress, many also report having derived benefits, or post-traumatic growth (PTG), from their cancer experience. This study examines PTG and its correlates among an ethnically diverse sample of adolescent/young adult (AYA) cancer survivors who have recently completed treatment. METHODS: Survivors of childhood cancer (n = 94; 47% Hispanic), ages 11-21 and within 6 months of completing cancer therapy, were recruited from three pediatric cancer centers. Participants completed a structured interview that assessed demographics, PTG, post-traumatic stress symptoms, health-related quality of life, optimism, and depressive symptoms. Diagnosis/treatment information was collected from each patient's medical record. Multiple regression analyses were used to identify significant correlates of PTG. RESULTS: The majority of survivors reported positive growth. PTG was positively associated with psychosocial functioning and post-traumatic stress symptoms and inversely associated with physical functioning and depressive symptoms. PTG was significantly lower among survivors of bone tumors (vs. survivors of other cancers) and Hispanic survivors who primarily spoke English at home (vs. Hispanics who primarily spoke Spanish at home and non-Hispanics). PTG was not significantly related to age, sex, optimism, cancer treatment modality, duration of treatment, or treatment intensity. CONCLUSIONS: The AYA survivors commonly reported PTG in the immediate aftermath of cancer treatment. Findings regarding PTG among more acculturated Hispanic and bone tumor AYA survivors may help to inform risk-adapted clinical interventions, among those transitioning from active treatment to post-treatment surveillance, to mitigate negative long-term sequelae and enhance positive psychosocial adaptation from the cancer diagnosis and treatment.

Prevalence and predictors of post-traumatic stress symptoms in adolescent and young adult cancer survivors: a 1-year follow-up study.

OBJECTIVES: Post-traumatic stress symptoms (PTSS) have been identified as a meaningful indicator of distress in cancer survivors. Distinct from young adult survivors of childhood cancer, young people diagnosed with cancer as adolescents and young adults (AYAs) face unique psychosocial issues; however, there is little published research of PTSS in the AYA population. This study examines prevalence and predictors of PTSS among AYAs with cancer. METHODS: As part of a longitudinal study of AYAs with cancer, 151 patients aged 15-39 years completed mailed surveys at 6 and 12 months post-diagnosis. Severity of PTSS was estimated at 6 and 12 months post-diagnosis. Multiple regression analyses were conducted to investigate the predictive effects of socio-demographic and clinical characteristics on changes in PTSS over time. RESULTS: At 6 and 12 months, respectively, 39% and 44% of participants reported moderate to severe levels of PTSS; 29% had PTSS levels suggestive of post-traumatic stress disorder. No significant differences in severity of PTSS between 6 and 12 months were observed. Regression analyses suggested that a greater number of side effects were associated with higher levels of PTSS at 6 months. Currently receiving treatment, having surgical treatment, diagnosis of a cancer type with a 90-100% survival rate, remaining unemployed/not in school, and greater PTSS at 6 months were associated with higher levels of PTSS at 12 months. CONCLUSIONS: Post-traumatic stress symptoms were observed as early as 6 months following diagnosis and remained stable at 12-month follow-up. The development of early interventions for reducing distress among AYA patients in treatment is recommended.

Mental health disparities between Hispanic and non-Hispanic parents of childhood cancer survivors.

BACKGROUND: Parents of childhood cancer survivors (CCS) experience considerable distress related to their child's cancer. However, little is known about cultural variation in this experience. We examine parental distress, specifically symptoms of post-traumatic stress (PTSS) and depression, comparing Hispanic and non-Hispanic parents of CCS. PROCEDURE: Seventy-nine Hispanic and 60 non-Hispanic parents of CCS (currently aged 14-25, off treatment ≥2 years) completed questionnaires assessing demographics, depression, PTSS, perceived stress, and child's health status/quality of life (QOL). t-Tests and chi-square statistics were used to compare differences in demographic characteristics between Hispanic and non-Hispanic parents and multivariable regression was used to determine independent risk factors associated with parental PTSS and depression. RESULTS: Hispanic parents were significantly younger, had less education, lower incomes and reported significantly more PTSS and depressive symptoms than non-Hispanic parents (all P-values < 0.0001). Among Hispanic parents, foreign birthplace predicted higher PTSS after controlling for other factors (P < 0.001). Hispanic parents, regardless of birthplace, reported more depressive symptoms than non-Hispanic parents (US-born, P < 0.05; foreign-born, P < 0.01). For PTSS and depression, there were positive relationships with parental stress and negative relationships with the child's psychosocial QOL. Hispanic and non-Hispanic CCS did not differ significantly on disease and treatment factors or health-related QOL. CONCLUSIONS: Hispanic parents of CCS may be at greater risk for poorer mental health outcomes. Ethnic-specific factors (e.g., acculturation, immigration status, and previous trauma) may influence parents' responses and adjustment to their child's cancer. Research is needed to determine how to meet the needs of the most vulnerable parents.

Perceived positive impact of cancer among long-term survivors of childhood cancer: a report from the childhood cancer survivor study.

OBJECTIVE: Investigations examining psychosocial adjustment among childhood cancer survivors have focused primarily on negative effects and psychopathology. Emergent literature suggests the existence of positive impact or adjustment experienced after cancer, as well. The purpose of this study is to examine the distribution of Perceived Positive Impact (PPI) and its correlates in young adult survivors of childhood cancer. METHODS: 6425 survivors and 360 siblings completed a comprehensive health survey, inclusive of a modified version of the Post-traumatic Growth Inventory (PTGI) as a measure of PPI. Linear regression models were used to examine demographic, disease and treatment characteristics associated with PPI. RESULTS: Survivors were significantly more likely than siblings to report PPI. Endorsement of PPI was significantly greater among female and non-white survivors, and among survivors exposed to at least one intense therapy, a second malignancy or cancer recurrence. Survivors diagnosed at older ages and fewer years since diagnosis were more likely to report PPI. Income, education and marital/relationship status appeared to have varied relationships to PPI depending upon the subscale being evaluated. CONCLUSIONS: The existence and variability of PPI in survivors in this study suggest that individual characteristics, inclusive of race, gender, cancer type, intensity of treatment, age at diagnosis and time since diagnosis, have unique and specific associations with different aspects of perceived positive outcomes of childhood cancer.

Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women.

Purpose Lymphedema of the arm is a potential complication of breast cancer therapy. This study examines pre-disposing factors that may operate in conjunction with treatment-related factors in the development of arm lymphedema in a large cohort of White and Black breast cancer survivors. Methods 494 women (271 White and 223 Black) with in situ to Stage III-A primary breast cancer completed a baseline interview within 18 months of diagnosis. Information on lymphedema was collected during a follow-up interview, conducted on average 50 months after diagnosis. Self-reported data were used to classify women with or without lymphedema. Multivariable logistic regression models were developed to identify risk factors for arm lymphedema. Results Arm lymphedema was associated with younger age at diagnosis (odds ratio, OR per year of age = 0.96; 95% confidence interval, CI = 0.93-0.99), positive history of hypertension (OR = 2.31; 95% CI = 1.38-3.88), obesity (OR for body mass index, BMI> or =30 = 2.48; 95% CI = 1.05-5.84) and having had surgery where 10 or more lymph nodes were excised (OR = 2.16; 95% CI = 1.12-4.17). While Black women had higher prevalence of arm lymphedema than White women (28% vs. 21%), race was not associated with lymphedema risk in models adjusted for multiple factors (adjusted OR = 1.01; 95% CI = 0.63-1.63). Conclusion Risk of arm lymphedema did not differ significantly for Black and White women. Risk factors identified in this study offer opportunities for interventions (weight loss, control of blood pressure, use of sentinel node biopsy where possible) for reducing incidence of lymphedema or controlling the symptoms associated with this condition.

Premature carotid artery disease in pediatric cancer survivors treated with neck irradiation.

BACKGROUND: While carotid artery disease and strokes have been documented in adult cancer patients treated with neck irradiation, little information is available on pediatric patients. The purpose of this study is to determine if carotid disease is more prevalent among pediatric cancer survivors treated with neck irradiation than among healthy controls. PROCEDURE: Thirty pediatric cancer survivors who received neck irradiation (2,000-6,660 cGy) and 30 healthy subjects underwent bilateral carotid ultrasounds. Study outcome measures were common carotid intima-media thickness (IMT) and plaque (present or absent). Multivariate methods were used to compare cases and controls and to identify risk factors related to carotid disease in childhood cancer survivors. RESULTS: IMT was greater for cancer survivors than controls (0.46 mm (SD 0.12) vs. 0.41 mm (SD 0.06), P < 0.001). Plaque was present in 18% of irradiated vessels and 2% of non-irradiated vessels (P < 0.01). Among cancer survivors, IMT was positively associated with female gender (P < 0.05), non-white ethnicity (P < 0.01), positive family history of stroke/heart attack (P < 0.05), BMI (P < 0.001), total cholesterol (P < 0.01), cancer relapse (P < 0.001), and years off treatment (P < 0.0001). Plaque was positively associated with relapse (P < 0.05) and C-reactive protein (P < 0.01). There was no significant relationship between radiation dose at levels >or=2,000 cGy and IMT or plaque. CONCLUSIONS: Carotid artery disease was more prevalent among cancer survivors treated with neck irradiation than among controls. Due to the high risk of stroke associated with advanced carotid disease, larger prospective studies are needed to better define disease risk in these long-term survivors.

Prevalence and correlates of fatigue in long-term survivors of childhood leukemia.

PURPOSE: To estimate the prevalence of fatigue, identify the factors associated with fatigue, and to explore the relationship between fatigue and quality of life (QOL) in long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: One hundred sixty-one ALL survivors diagnosed at Childrens Hospital Los Angeles (Los Angeles, CA) before age 18 years and between January 1, 1975 and December 31, 1995, participated in a structured telephone interview. Participants were aged 18 to 41 years and off treatment for an average of 14 years. Four measures of fatigue, including the Revised-Piper Fatigue Scale, were used to assess fatigue; depression was assessed using the Center for Epidemiological Studies Depression Scale. Multivariate logistic regression models were developed to identify factors associated with fatigue and depression. RESULTS: Prevalence of fatigue (30%) fell within the general population normal limits. Fatigue and depression were highly correlated (Pearson r = 0.75). Fatigue was associated with marriage (OR = 0.11; 95% CI, 0.02 to 0.50), having children (OR = 5.80; 95% CI, 1.30 to 25.82), sleep disturbances (OR = 6.15; 95% CI, 2.33 to 16.22), pain (OR = 5.56; 95% CI, 2.13 to 14.48), obesity (OR = 3.80; 95% CI, 1.41 to 10.26), cognitive impairment (OR = 2.56; 95% CI, 1.02 to 6.38), and exercise-induced symptoms (OR = 2.98; 95% CI, 1.11 to 8.02). Four factors associated with fatigue were also associated with depression: sleep disturbances, pain, obesity, and cognitive impairment. Fatigue was inversely related to QOL. CONCLUSION: Some survivors of childhood ALL experience fatigue many years after treatment. Fatigued survivors represent a high-risk subgroup as they report more depression and poorer QOL than non-fatigued survivors and their peers.

Reconsidering Physical Activity Restrictions for Mononephric Survivors of Childhood Cancer: A Report From the Children's Oncology Group.

Although traditional recommendations for mononephric childhood cancer survivors are to avoid contact sports in order to protect the remaining kidney, review of available evidence suggests that the majority of renal loss is caused by accidents not involving sports. An interdisciplinary team performed a review of the English literature published from 1999 to 2012 within the PubMed, Cochrane, Google Scholar, and National Guidelines Clearinghouse databases. The level of evidence and proposed recommendations were graded according to an established rubric and GRADE criteria. Our review found that kidney loss is most commonly caused by nonsports activities such as motor vehicle accidents and falls, implying that restrictions on sports-related activity in mononephric pediatric survivors are not well supported. This favors encouraging ordinary sports and related activities without restriction in mononephric childhood cancer survivors because the known benefits of exercise outweigh the exceedingly low risk of renal loss. Accordingly, activity recommendations for mononephric patients have been revised in the most current version of the Children's Oncology Group Long-term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. This has important implications for this and similar populations who may now undertake individual and organized sports without undue regard for their mononephric status.

Individual prediction of heart failure among childhood cancer survivors.

PURPOSE: To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer. PATIENTS AND METHODS: Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models. RESULTS: Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%). CONCLUSION: Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions.

Trajectories of psychological distress in adolescent and young adult patients with cancer: a 1-year longitudinal study.

PURPOSE: To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and clinical predictors of changes in distress were examined. PATIENTS AND METHODS: In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18). RESULTS: Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress. CONCLUSION: Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.

Exercise recommendations for childhood cancer survivors exposed to cardiotoxic therapies: an institutional clinical practice initiative.

Childhood cancer survivors who have received treatment with anthracyclines are at risk for developing cardiomyopathy in dose-dependent fashion. Historically, restrictions on certain types of physical activity that were intended to preserve cardiac function have been recommended, based on a mixture of evidence-based and consensus-based recommendations. In the LIFE Cancer Survivorship & Transition Program at Children's Hospital Los Angeles, the authors reevaluated their recommendations for exercise in survivors who were exposed to anthracyclines, with or without irradiation in proximity to the myocardium. The primary goal was to develop consistent, specific, practical, safe, and (where possible) evidence-based recommendations for at-risk survivors in the program. To accomplish this, the authors referred to current exercise guidelines for childhood cancer survivors, consulted recent literature for relevant populations, and obtained input from the program's pediatric cardiology consultant. The resulting risk-based exercise recommendations are designed to complement current published guidelines, maximize safe exercise, and help childhood cancer survivors return to a normal life that emphasizes overall wellness and physical activity. This article describes a single institution's experience in modifying exercise recommendations for at-risk childhood survivors and includes the methods, findings, and current institutional practice recommendations along with sample education materials.

Cancer survivor identity shared in a social media intervention.

This study investigates how cancer survivors construct their identities and the impact on their psychological health, as measured by depression and survivor self-efficacy. Fourteen young adult survivors of pediatric cancer participated in a customized social networking and video blog intervention program, the LIFECommunity, over a 6-month period. Survivors were asked to share their stories on various topics by posting video messages. Those video blog postings, along with survey data collected from participants, were analyzed to see how cancer survivors expressed their identities, and how these identities are associated with survivors' psychosocial outcomes. In survivors who held negative stereotypes about cancer survivors, there was a positive relationship with depression while positive stereotypes had a marginal association with cancer survivor efficacy. Findings indicate that although pediatric cancer survivors often do not publicly discuss a "cancer survivor identity," they do internalize both positive and negative stereotypes about cancer survivorship. It is important for practitioners to be aware of the long-term implications of cancer survivor identity and stereotypes.

Defining medical posttraumatic stress among young adult survivors in the Childhood Cancer Survivor Study.

OBJECTIVE: To examine the implications of use of differential thresholds for studying medical Posttraumatic Stress Disorder (PTSD). METHODS: Self-report data from 6,542 young adult survivors of childhood cancer and 374 of their siblings were used to create clearly differentially defined groups to compare prevalence, correlations and predictors of posttraumatic stress. RESULTS: Prevalence of posttraumatic stress in survivors compared to siblings differed by definition used, ranging from an odds ratio of 4.21 (95% CI 2.11-8.38) when posttraumatic stress was defined as meeting full symptoms plus functional impairment to 1.42 (95% CI 0.79-2.56) for partial symptoms with functional impairment. Re-experiencing symptoms did not substantially contribute to the ability to identify functional impairment and emotional distress. Although most of the variables associated with posttraumatic stress symptoms and impairment were consistent across definitions of PTSD, marital status and employment demonstrated nonproportional relationships. CONCLUSIONS: Choice of the definition used in studying posttraumatic stress after serious illness alters not only epidemiological findings, but also associations with correlates and predictors. This is important in the current debate about the criteria for PTSD in the upcoming DSMV. Further study is needed to determine if these findings are applicable to people exposed to other types of traumatic events.

Prevalence and predictors of posttraumatic stress disorder in adult survivors of childhood cancer.

OBJECTIVE: This study compared the prevalence of symptoms of posttraumatic stress disorder (PTSD), with functional impairment and/or clinical distress, among very long-term survivors of childhood cancer and a group of healthy siblings. METHODS: A total of 6542 childhood cancer survivors >18 years of age who received diagnoses between 1970 and 1986 and 368 siblings of cancer survivors completed a comprehensive demographic and health survey. RESULTS: A total of 589 survivors (9%) and 8 siblings (2%) reported functional impairment and/or clinical distress in addition to the set of symptoms consistent with a full diagnosis of PTSD. Survivors had more than fourfold greater risk of PTSD, compared with siblings (odds ratio [OR]: 4.14 [95% confidence interval [CI]: 2.08-8.25]). With controlling for demographic and treatment variables, increased risk of PTSD was associated with educational level of high school or less (OR: 1.51 [95% CI: 1.16-1.98]), being unmarried (OR: 1.99 [95% CI: 1.58-2.50]), having annual income below $20,000 (OR: 1.63 [95% CI: 1.21-2.20]), and being unemployed (OR: 2.01 [95% CI: 1.62-2.51]). Intensive treatment also was associated with increased risk of full PTSD (OR: 1.36 [95% CI: 1.06-1.74]). CONCLUSIONS: PTSD was reported significantly more often by survivors of childhood cancer than by sibling control subjects. Although most survivors apparently are faring well, a subset reported significant impairment that may warrant targeted intervention.

The role of the long-term follow-up clinic in discovering new emerging late effects in adult survivors of childhood cancer.

Our understanding of late effects in long-term survivors of childhood cancer is continually evolving as significant numbers of survivors are entering middle to later adulthood. Effects of conventional treatment on premature aging are being recognized, as are long-term effects of newer therapies. Clinicians in long-term follow-up clinics are in a unique position to monitor for recognized late effects and to be alert to signs and symptoms of late effects that have not been previously reported in the pediatric cancer literature. This article presents 2 young adult survivors who displayed subtle signs of impaired cerebral blood flow due to carotid artery stenosis many years after being treated with neck irradiation. When the first patient presented nearly a decade ago in the clinic with symptoms, premature carotid artery disease was not a radiation-related late effect that had been reported previously in survivors of childhood cancer. These cases are used to illustrate the key role of long-term follow-up clinics in identifying new and emerging treatment-related late effects and underscore the importance of lifetime surveillance and the need for collaboration between pediatric and adult health care providers.

Factors associated with health-related quality of life in pediatric cancer survivors.

BACKGROUND: Childhood cancer survivors are at risk for late effects of disease and treatment that may be attributed to multiple causes. This study describes health-related quality of life (HRQOL) in childhood cancer survivors and identifies factors related to poor quality of life outcomes. PROCEDURE: Patients age 8-18 years, who attended the long-term information, follow-up, and evaluation (LIFE) clinic at Childrens Hospital Los Angeles during a 1-year time-period were eligible for the study. Eighty-six survivors (mean time off-treatment=7.8 years) completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scales, a LIFE Clinic Intake Questionnaire and rated their fatigue using a 10-point scale. Oncology nurses independently rated subjects' late effects using a 3-point severity scale. Linear regression procedures were used to evaluate the association between demographic and medical factors and HRQOL. RESULTS: Fatigue and more severe late effects were associated with poorer physical functioning (fatigue, P<0.02; late effects, P<0.01). Fatigue, ethnic minority status, and a brain tumor diagnosis were associated with poorer psychosocial functioning (fatigue, P<0.0001; minority status, P<0.04; brain tumor, P<0.01). Fatigue was the only factor related to both poor physical and psychosocial HRQOL. CONCLUSIONS: Long-term follow-up clinics for childhood cancer survivors are in a unique position to monitor HRQOL over time. Factors associated with poorer HRQOL include fatigue, ethnic minority status, a brain tumor diagnosis, and more severe late effects. Future studies need to clarify relationships between ethnicity, socioeconomic status (SES), and HRQOL in cancer survivors.

The PedsQL Brain Tumor Module: initial reliability and validity.

BACKGROUND: Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5-year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module. METHODS: The PedsQL 4.0 Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range=2-18 years). The sample included children with tumors located in the posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12 months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34, 34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%), chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS: Internal consistency reliability was demonstrated for the 24-item PedsQL Brain Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale. CONCLUSIONS: The findings provide support for the measurement properties of the PedsQL Brain Tumor Module.